Gilman cuprates, reactions

Since the preformed aggregate Bu3Cu2Li showed a diastereoselectivity of 83 17 in the presence of boron trifluoride16, the low diastereoselectivity noted above was presumably due to a faster addition reaction of butyllithium, which is formed by the treatment of the Gilman cuprate with the boron trifluoride-diethyl ether complex16,, s. 

The discovery of the Gilman cuprate Me2CuLi [5-8], and House s [6, 7] and Corey s [8] demonstrations of its synthetic potential, produced a major breakthrough in this area of chemistry. A major disadvantage of the application of this type of cuprate reagents in stoichiometric amounts, especially from the point of view of atom economy , is the fact that one equivalent of the (potentially valuable) organic component is usually not used in the reaction and ends up as chemical... 

A drawback of the Z enoates is usually lower reactivity, reflected in prolonged reaction times and higher reaction temperatures. This may be overcome by switching to more reactive enone systems. Thus, addition of the functionalized cyano-Gilman cuprate system 67 to Z enone 66 proceeded smoothly at low temperatures, with excellent acyclic stereocontrol at the /i-stereocenter [26, 27]. Stereocontrol upon... 

In the 1952 paper mentioned above [3], Gilman reported on the formation of lithium dimethylcuprate from polymeric methylcopper and methyllithium. These so-called Gilman cuprates were later used for substitution reactions on both saturated [6] and unsaturated [7, 8, 9] substrates. The first example of a cuprate substitution on an allylic acetate (allylic ester) was reported in 1969 [8], while Schlosser reported the corresponding copper-catalyzed reaction between an allylic acetate and a Grignard reagent (Eq. 2) a few years later [10]. 

Solution Tlie first reaction leads under basic conditions to cyclization to epoxide 34. Replacement of the triflate group by a methyl group to give 35 is accomplished with the aid of a Gilman cuprate.11 The... 

The enoates 17 were obtained in good yield and diastereoselectivity by subjecting the crude hydroformylation products 6 to Horner-Wadsworth-Emmons olefination conditions (HWE). Reaction of enoates 17 with dialkyl Gilman cuprates gave the anti 1,4-addition... 

So far only little is known about the mechanisms of such 1,4-additions. To start with, it is uncertain whether they only depend on the metal used or on both metal and substrate. At the beginning of the new millennium, however, the prototype of this reaction, i.e., the 1,4-addition of Gilman cuprates to a,fi-unsaturated ketones, could finally be assigned a mechanism after many years of studies and with a proper finish of crystallographic, NMR-spectroscopic, kinetic and quantum-chemical studies (Figure 10.46, see farther below). 

Fig. 10.46. Mechanistic possibilities for the 1,4-addition of a Gilman cuprate to an a,/f-unsaturated ketone. Part 1 shows the reaction up to the rate-determining step (F -> G). For the sake of greater clarity the solvation of the lithium atoms is left unconsidered here.

Tab. 16.1 Product Spectrum of C,C Coupling Reactions with the Gilman Cuprate Me2CuLi. Analogous products are obtained with the Gilman cuprates R2CuLi, where R can bean alkyl (= Me), alkenyl or aryl substituent...

Fig. 16.1. Presumed elementary steps of a C,C coupling between a Gilman cuprate and an alkenyl or aryl triflate (X = 03S—CF3), bromide (X = Br), or iodide (X = I). The four elementary steps of the reaction, discussed in the text, are (1) complexation, (2) oxidative addition of the substrate to the metal, (3) reductive elimination, and (4) dissociation of the w-bound ligand.

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